A High-Na+ Conduction State during Recovery from Inactivation in the K+ Channel Kv1.5

Wang, Zhuren; Hesketh, J. Christian; Fedida, David

doi:10.1016/s0006-3495(00)76486-1

Cited by 34 publications

(80 citation statements)

References 35 publications

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“…Our experimental data show that inactivation in full-length Kv1.5, as in most voltage-gated K + channels, increases with voltage and eventually stabilizes, so that the inactivation-voltage relationship reaches a basal level at depolarized potentials. In Kv1.5, for very long pulses this is at ∼40% of the maximum current (Fedida et al 1999); although, it should be noted that inactivation can be almost complete when Na + permeates the channel (Wang et al 2000). In Kv1.5ΔN209, inactivation shows a prominent upturn when studied in both HEK 293cells and mouse L cells (Fig.…”

Section: Discussionmentioning

confidence: 99%

Altered State Dependence of C-Type Inactivation in the Long and Short Forms of Human Kv1.5

Kurata

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Fedida

2001

The Journal of General Physiology

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Evidence from both human and murine cardiomyocytes suggests that truncated isoforms of Kv1.5 can be expressed in vivo. Using whole-cell patch-clamp recordings, we have characterized the activation and inactivation properties of Kv1.5ΔN209, a naturally occurring short form of human Kv1.5 that lacks roughly 75% of the T1 domain. When expressed in HEK 293 cells, this truncated channel exhibited a V1/2 of −19.5 ± 0.9 mV for activation and −35.7 ± 0.7 mV for inactivation, compared with a V1/2 of −11.2 ± 0.3 mV for activation and −0.9 ± 1.6 mV for inactivation in full-length Kv.15. Kv1.5ΔN209 channels exhibited several features rarely observed in voltage-gated K+ channels and absent in full-length Kv1.5, including a U-shaped voltage dependence of inactivation and “excessive cumulative inactivation,” in which a train of repetitive depolarizations resulted in greater inactivation than a continuous pulse. Kv1.5ΔN209 also exhibited a stronger voltage dependence to recovery from inactivation, with the time to half-recovery changing e-fold over 30 mV compared with 66 mV in full-length Kv1.5. During trains of human action potential voltage clamps, Kv1.5ΔN209 showed 30–35% greater accumulated inactivation than full-length Kv1.5. These results can be explained with a model based on an allosteric model of inactivation in Kv2.1 (Klemic, K.G., C.-C. Shieh, G.E. Kirsch, and S.W. Jones. 1998. Biophys. J. 74:1779–1789) in which an absence of the NH2 terminus results in accelerated inactivation from closed states relative to full-length Kv1.5. We suggest that differential expression of isoforms of Kv1.5 may contribute to K+ current diversity in human heart and many other tissues.

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Section: Discussionmentioning

confidence: 99%

Altered State Dependence of C-Type Inactivation in the Long and Short Forms of Human Kv1.5

Kurata

Soon

Fedida

2001

The Journal of General Physiology

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“…Several studies showed that substantial Na + can permeate animal Shaker K + channels at very positive potentials; this Na + permeation is often most prominent in the C-type inactivated state of the channels (Callahan and Korn 1994;Kiss et al 1998;Kiss et al 1999;Lopez-Barneo et al 1993;Ogielska and Aldrich 1998;Starkus et al 2000;Starkus et al 1997;Wang et al 2000;Yellen 1998). …”

Section: Cortical Cells Of Rootsmentioning

confidence: 99%

Mechanisms of sodium uptake by roots of higher plants

2009

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The negative impact of soil salinity on agricultural yields is significant. For agricultural plants, sensitivity to salinity is commonly (but not exclusively) due to the abundance of Na + in the soil as excess Na + is toxic to plants. We consider reducing Na + uptake to be the key, as well as the most efficient approach, to control Na + accumulation in crop plants and hence to improve their salt resistance. Understanding the mechanism of Na + uptake by the roots of higher plants is crucial for manipulating salt resistance. Hence, the aim of this review is to highlight and discuss recent advances in our understanding of the mechanisms of Na + uptake by plant roots at both physiological and molecular levels. We conclude that continued efforts to investigate the mechanisms of root Na + uptake in higher plants are necessary, especially that of low-affinity Na + uptake, as it is the means by which sodium enters into plants growing in saline soils.

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“…Data in Fig. 6A show currents recorded during a 1-s depolarizing pulse to ϩ60 mV from mutant channels in which the arginine at position 487 in the outer pore was replaced with a valine (R487V) [this is equivalent to the T499V mutation in Shaker (Lopez-Barneo et al, 1993;Wang et al, 2000)]. R487V mutant channels showed little inactivation during the pulse, and the effect of 1 M KN-93 was significantly reduced (Fig.…”

Section: Kn-93 Delays Recovery From Inactivation Data Inmentioning

confidence: 99%

KN-93 (2-[N-(2-Hydroxyethyl)]-N-(4-methoxybenzenesulfonyl)]amino-N-(4-chlorocinnamyl)-N-methylbenzylamine), a Calcium/Calmodulin-Dependent Protein Kinase II Inhibitor, Is a Direct Extracellular Blocker of Voltage-Gated Potassium Channels

Rezazadeh

Claydon²,

Fedida³

2005

J Pharmacol Exp Ther

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108

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The effect of Ca 2ϩ /calmodulin-dependent protein kinase II (CaMK II) on voltage-gated ion channels is widely studied through the use of specific CaMK II blockers such as 2-[N-(2-hydroxyethyl)]-N-(4-methoxybenzenesulfonyl)]amino-N-(4-chlorocinnamyl)-N-methylbenzylamine (KN-93). The present study demonstrates that KN-93 is a direct extracellular blocker of a wide range of cloned Kv channels from a number of different subfamilies. In all channels tested, the effect of 1 M KN-93 was independent of CaMK II because 1 M 2-[N-(4-methoxybenzenesulfonyl)]amino-N-(4-chlorocinnamyl)-N-methylbenzylamine, phosphate (KN-92), an inactive analog of KN-93, caused similar inhibition of currents. In addition, dialysis of cells with 10 M CaMK II inhibitory peptide fragment 281-301 (CIP) had no effect on current kinetics and did not prevent the inhibitory effect of KN-93. The IC 50 for block of the Kv1.5 channel (used as an example to determine the nature of KN-93 block) was 307 Ϯ 12 nM. KN-93 blocked open channels with little voltage dependence that did not alter the V 1/2 of channel activation. Removal of P/C-type inactivation by mutation of arginine 487 to valine in the outer pore region of Kv1.5 (R487V) greatly reduced KN-93 block, whereas enhancement of inactivation induced by mutation of threonine 462 to cysteine (T462C) increased the potency of KN-93 by 4-fold. This suggested that KN-93 acted through promotion and stabilization of C-type inactivation. Importantly, KN-93 was ineffective as a blocker when applied intracellularly, suggesting that CaMK II-independent effects of KN-93 on Kv channels can be circumvented by intracellular application of KN-93.Voltage-gated potassium (Kv) channels, which are activated by changes in the transmembrane potential, play an important role in the control of excitability. There are a number of structurally related subfamilies of Kv channels (Chandy, 1991) that are expressed in a wide range of tissues, such as heart [e.g., Kv1, Kv2, Kv4, and human ether a-go-go-

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A High-Na+ Conduction State during Recovery from Inactivation in the K+ Channel Kv1.5

Cited by 34 publications

References 35 publications

Altered State Dependence of C-Type Inactivation in the Long and Short Forms of Human Kv1.5

Altered State Dependence of C-Type Inactivation in the Long and Short Forms of Human Kv1.5

Mechanisms of sodium uptake by roots of higher plants

KN-93 (2-[N-(2-Hydroxyethyl)]-N-(4-methoxybenzenesulfonyl)]amino-N-(4-chlorocinnamyl)-N-methylbenzylamine), a Calcium/Calmodulin-Dependent Protein Kinase II Inhibitor, Is a Direct Extracellular Blocker of Voltage-Gated Potassium Channels

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